title: Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model.
abstract: Many attempts to demonstrate the oncogenic role of the JC virus (JCV) have been partially successful in producing brain tumors, either by direct inoculation of JCV into the brain or in transgenic models in rodents. We previously reported the presence of JCV DNA with a relatively high incidence in pulmonary and digestive organs. However, we could not prove the oncogenic role of JCV. We prepared a transgene composed of the K19 promoter, specific to bronchial epithelium with the JCV T-antigen and established transgenic (TG) mice. Pulmonary tumors were detected without any metastasis in 2 out of 15 (13.3%) 16-month-old K19/JCV T-antigen TG mice. Using immunohistochemistry (IHC), these tumors showed JCV T-antigen, p53 and CK 19 expression, but not expression of nuclear and cytoplasmic β-catenin and insulin receptor substrate 1 (IRS1). IHC revealed the same expression pattern as in the bronchial epithelium of the TG mice. One tumor, which was examined with laser capture microdissection and molecular biological tools, demonstrated an EGFR mutation but not a K-ras mutation. We propose that the pulmonary tumors were derived from the JCV T-antigen in a TG mouse model. These findings shed light on pulmonary carcinogenesis.
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa 241-0815, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Noguchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohtsu
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Yoshiwara
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Huachuan
authors.initials: H
authors.lastname: Zheng
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis; D007577:JC Virus / Q000235:genetics / Q000472:pathogenicity*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D000957:Antigens, Viral, Tumor; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D051176:beta Catenin